This STTR grant proposal is for the development of a safe and efficacious Anthrax Toxin Vaccine. The present world-wide threat of the use of anthrax spores as a bioterrorist weapon in military theaters as well as on the general population has focused attention on the need for a more effective vaccine against anthrax. The recognition during the past few months that few members of the medical community have seen an anthrax infection in humans and therefore only a very few are equipped to diagnose and treat anthrax. The availablity of a safe and efficacious prophylactic vaccine would effectively neutralize this form of bioterrorist threat. Price, et al., have shown that a vaccine comprised of plasmid DNAs encoding detoxified protective antigen (PA) and lethal factor (LF) protects mice from an intravenous challenge using 5X the lethal dose of toxic protein. Based on this work and subsequent work (presented here) showing that a similar DNA vaccination protocol can protect rabbits from a more rigorous spore inhalation challenge, this grant proposes the pre-clincal work required to support testing of a DNA vaccine in human clinical trials. The work would advance an FDA approved plasmid DNA vector encoding the the PA or LF plasmids or a formulation combining the PA + LF plasmids through a series of experimental protocols to demonstrate the generation of a protective immunne response in both mice and rabbits. The thrust of this proposal is to determine the best plasmid to deliver these coding sequences, the best formulation for intramuscular delivery, and the best injection regime and dosage for achieving protection in a large mammal This work demonstrates the best use of STTR funding. It brings together Vical, the company which has advanced DNA vaccination technology over the past 12 years and holds the intellectural property required to make DNA vaccines commercial products, with Dr. Darrell Galloway, a professor at Ohio State University and a researcher who has advanced the use of DNA vaccines against anthrax. The proposal also presents how the combined efforts of an academic laboratory with the expertise, animal facilities, and reagents required for these pre-clinical experiments and a small biotechnology company expert in the development of DNA vaccines, can work together to quickly advance this novel vaccine technology into the clinic.